We propose to create a Berkeley Nanomedicine Development Center in Membrane Signaling. The research focus of the Center will be on the biomolecular dynamics of signaling proteins and the operation of signaling networks. Our goal is to elucidate the mechanism of function of receptors in the plasma membrane, which sense signals in the external environment, and of the web of intracellular enzymes to which the membrane receptors relay their signals. Cellular signaling is fundamental to processes as varied as chemical sensation, information processing in the nervous and immune systems, and gene regulation. G-protein coupled receptors and protein kinases, on which much of the effort will focus, represent two of the largest protein families in the human genome. We propose a novel approach to the study of signaling, which we think will revolutionize how cell biology is done and how the function of individual proteins is assessed and controlled in tissues. This is an area of great significance for medicine because of the importance of receptors and kinases as therapeutic targets and because of the seriousness of illness caused by their mutation. Several innovative approaches developed at Berkeley will be deployed. This provide for unprecendented precision in the ability to monitor and manipulate the function of signaling proteins in their natural membrane and cell environments and in the context of complex signaling networks.